The goal of our proposed study is to investigate whether a transient period of diabetes remission after roux-en- y gastric bypass surgery (RYGB) induces a sustained benefit in long-term microvascular and macrovascular disease outcomes. Our project would be an expansion of our recent research in this area in which we utilize electronic medical record data from four large, integrated health plans and care delivery systems in the HMO Research Network (HMORN) to examine short and long-term health outcomes of over 9,000 severely obese individuals with type 2 diabetes who have undergone RYGB over an 18-year period (1996-2014). The longitudinal cohorts and rich, clinical and administrative data available at these HMORN sites are crucial for conducting valid, robust longitudinal studies of bariatric surgery because extensive adjustments, stratification, and sub-setting that are required. For our new application presented here, we propose to extend and expand our prior cohort in terms of size, duration of follow-up, and the number of clinically-important outcomes addressed. We will increase the follow- up period for our initial cohort by six years to further improve our ability to characterize the longer-term complications of diabetes. We will increase the size of our cohort by tapping a previously unutilized data source - H1,000 adults with diabetes who received RYGB at Group Health Cooperative. Finally, our major innovation will be to explore the legacy effect of RYGB through a series of analyses that characterize long- term, micro- and macrovascular outcomes across three patient groups: those who do not remit their diabetes after RYGB;those who experience durable diabetes remission after RYGB;and those who relapse their diabetes after an initial remission. Microvascular outcomes will include the following: (i) renal disease: decreased glomerular filtration rate and micro/macroalbuminura;and (ii) eye disease: diabetic retinopathy and clinically significant macular edema. Macrovascular outcomes will include the following: (i) cardiac ischemia, infarction, angioplasty/stent, or coronary bypass surgery;(ii) stroke or transient ischemic attack and (iii) peripheral vascular disease-related ulceration, revascularization or amputation This study will test the following novel hypotheses: (1) severely obese patients who experience a durable remission of diabetes after RYGB will have fewer incident microvascular and macrovascular complications compared to those who do not remit their diabetes, (2) the beneficial effects of a transient period of diabetes remission after RYGB will persist after diabetes relapse (legacy effect);i.e., relapsing patients will experience fewer complications than those who do not remit their diabetes after RYGB, and (3) the duration of diabetes remission and/or control after RYGB will be significantly associated with the risk of incident microvascular and macrovascular complications.

Public Health Relevance

The UKPDS and the DCCT studies have previously shown that transient periods of relatively better glycemic control resulted in significant long-term benefits in terms of reduced microvascular and macrovascular complications, even though the levels of glycemic control eventually became identical between intervention and control subjects when the randomization period ended. The prolonged beneficial effects of improved glycemic control observed in these studies have been termed the legacy effect or metabolic memory. The goal of our proposed study is to investigate whether there is a legacy effect induced by bariatric surgery.